Studies were performed to examine the maturation and regulation of the human immune response in normal individuals and in patients with congenital and acquired immune deficiency states associated with a high frequency of cancer. The interaction of the T-cell derived lymphokine interleukin-2 IL-2) with its cell membrane receptor (IL-2R) plays a pivotal role in the establishment and maturation of the immune response. Soluble Tac protein from the human IL-2R is released from activated T-cells, B-cells, and monocytes in vitro and is also constitutively produced by leukemic cells in vitro. This soluble Tac protein is 10 kDa smaller than the Tac protein expressed on cell surfaces and specifically binds IL-2 with low affinity (20 nM). Soluble Tac protein was measurable by a double epitope enzyme-linked immunoassay (ELlSA) in the serum and urine but not cerebrospinal fluid of all normal individuals. Elevated levels of soluble Tac protein were found in the serum of several retroviral associated diseases including the adult T-cell leukemia (ATL), hairy cell leukemia (HCL), and the acquired immune deficiency syndrome (AIDS). Favorable responses to therapy in ATL and HCL were associated with reductions in serum Tac protein. Among patients with non-Hodgkin's lymphoma, the serum level of Tac protein at the time of diagnosis was the best predictor of survival following therapy. Serum Tac protein was also elevated at the time of rejection episodes in liver and heart-lung transplant recipients and in patients with active sarcoidosis. Measurement of Tac protein in serum is useful in the diagnosis and management of certain cancer patients and in monitoring the state of immunologic activation in humans in vivo.